9CD9

Structure of type II-2 alpha-synuclein filament from multiple system atrophy

9CD9 の概要

• エントリーDOI: 10.2210/pdb9cd9/pdb
• 関連するPDBエントリー: 9CDA
• EMDBエントリー: 45464 45465
• 分子名称: Alpha-synuclein (1 entity in total)
• 機能のキーワード: fibril, synuclein, protein fibril
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 22
• 化学式量合計: 318474.38

構造登録者

Yan, N.L.,Candido, F.,Tse, E.,Melo, A.A.,Southworth, D.R.,Merz, G.E. (登録日: 2024-06-24, 公開日: 2024-11-27, 最終更新日: 2025-01-22)

主引用文献

Yan, N.L.,Candido, F.,Tse, E.,Melo, A.A.,Prusiner, S.B.,Mordes, D.A.,Southworth, D.R.,Paras, N.A.,Merz, G.E.
Cryo-EM structure of a novel alpha-synuclein filament subtype from multiple system atrophy.
Febs Lett., 599:33-40, 2025

PubMed Abstract: Multiple system atrophy (MSA) is a progressive neurodegenerative disease characterized by accumulation of α-synuclein cross-β amyloid filaments in the brain. Previous structural studies of these filaments by cryo-electron microscopy (cryo-EM) revealed three discrete folds distinct from α-synuclein filaments associated with other neurodegenerative diseases. Here, we use cryo-EM to identify a novel, low-populated MSA filament subtype (designated Type I) in addition to a predominant class comprising MSA Type II filaments. The 3.3-Å resolution structure of the Type I filament reveals a fold consisting of two asymmetric protofilaments, one of which adopts a novel structure that is chimeric between two previously reported protofilaments. These results further define MSA-specific folds of α-synuclein filaments and have implications for designing MSA diagnostics and therapeutics.

PubMed: 39511911
DOI: 10.1002/1873-3468.15048

実験手法

ELECTRON MICROSCOPY (3.2 Å)